scholarly journals What is Standard Dose of Rivaroxaban in Elderly Asian Patients with Atrial Fibrillation: 20ms versus. 15mg?

2021 ◽  
Vol 27 ◽  
pp. 107602962110611
Author(s):  
Sung Soo Kim ◽  
Ki Hong Lee ◽  
Nam Sik Yoon ◽  
Hyung Wook Park ◽  
Jeong Gwan Cho
Keyword(s):  
Atrial Fibrillation ◽  
Elderly Patients ◽  
Dose Reduction ◽  
Major Bleeding ◽  
Standard Dose ◽  
Comparable Efficacy ◽  
Systemic Embolism ◽  
Off Label ◽  
Korean Patients ◽  
Asian Patients

Although there is no age criterion for rivaroxaban dose reduction, elderly patients with atrial fibrillation (AF) are often prescribed an off-label reduced dose. We aimed to evaluate whether age is a necessary criterion for rivaroxaban dose reduction in Korean patients with AF. Among 2208 patients who prescribed warfarin or rivaroxaban, 552 patients over 75 years without renal dysfunction (creatinine clearance >50 mL/min) were compared based on propensity score matching. The rivaroxaban group was further divided into a 20 mg (R20; on-label) and a 15 mg (R15; off-label). Primary net clinical benefit (NCB) was defined as the composite of stroke, systemic embolism, major bleeding, and all-cause mortality. Secondary NCB was defined as the composite of stroke, systemic embolism, and major bleeding. Patients were followed for 1 year, or until the first outcome occurrence. Both rivaroxaban groups had comparable efficacy compared with warfarin. However, both R20 (0.9% vs 7.4%, p = .014) and R15 (2.3% vs 7.4%, p = .018) had a significant reduction in major bleeding. There were no differences in efficacy or safety outcomes between R20 and R15. R20 had significantly reduced primary (hazard ratio [HR] 0.33, 95% confidence interval [CI]: 0.12–0.93) and secondary (HR 0.31, 95% CI: 0.10–0.93) NCBs compared with warfarin. However, primary and secondary NCBs were not reduced in R15. In real-world practice with elderly patients with AF, off-label rivaroxaban dose reduction to 15 mg conferred no benefits. Therefore, guideline-adherent rivaroxaban 20 mg is favorable in elderly Korean patients with AF.

P279 Standard dose of rivaroxaban in Asian patients with atrial fibrillation: 20ms vs.15mg? Off label dose reduction of rivaroxaban should be avoided

2020 ◽  
Vol 41 (Supplement_1) ◽  
Author(s):  
H K Jeong ◽  
J M Won ◽  
K H Lee ◽  
N S Yoon ◽  
H W Park ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Dose Reduction ◽  
Major Bleeding ◽  
Standard Dose ◽  
Comparable Efficacy ◽  
Systemic Embolism ◽  
Off Label ◽  
Safety Outcome ◽  
Asian Patients ◽  
Net Clinical Benefit

Abstract Background Rivaroxaban emerged as potential alternatives to warfarin for the prevention of thromboembolisim in patients with atrial fibrillation (AF). Because of the concern for the risk of major bleeding with rivaroxaban in Asian patients, off label rivaroxaban dose reduction to15mg is common in Asian real-world practice. We aimed to set standard rivaroxaban dose in Asian patients with AF by comparison between on-label rivaroxaban 20mg and off-label reduced rivaroxaban dose 15mg. Methods A total of 2,208 consecutive non-valvular AF patients were enrolled between 2011 and 2017. After propensity score matching, both warfarin (n = 804) and rivaroxaban group (n = 804) had comparable baseline characteristics. Rivaroxaban group was further divided into on-label rivaroxaban 20mg group (n = 390) and off-label reduced rivaroxaban 15mg group (n = 333). Efficacy outcome was stroke/systemic embolism. Safety outcome was major bleeding. Primary net clinical benefit (NCB) was defined as the composite of stroke, systemic embolism, major bleeding and all-cause mortality. Secondary NCB was defined as the composite of stroke, systemic embolism and major bleeding. Patients were followed upto one-year or until the first occurrence of any study outcomes. Results Both Rivaroxaban groups had comparable efficacy compared to warfarin. However, both on-label rivaroxaban 20mg (hazard ratio [HR] 0.40, 95% confidence interval [CI] 0.18-0.90, p = 0.026) and off-label reduced rivaroxaban 15mg (HR 0.37, 95% CI 0.16-0.88, p = 0.025) significantly reduced major bleeding. There were no differences in efficacy and safety outcomes between on-label rivaroxaban 20mg and off-label reduced rivaroxaban 15mg group. On-label rivaroxaban 20mg significantly reduced primary (HR 0.44, 95% CI 0.25-0.79, p = 0.006) and secondary (HR 0.51, 95% CI 0.27-0.96, p = 0.038) NCBs compared to warfarin. However, off-label reduced rivaroxaban 15mg did not reduce both primary and secondary NCBs. Conclusion Off-label rivaroxaban dose reduction to 15mg had no benefit compared to on-label rivaroxaban 20mg. Compared to warfarin, on-label rivaroxaban 20mg significantly improved primary and secondary NCBs, whereas off-label reduced rivaroxaban 15mg did not. Therefore, rivaroxaban 20mg is favorable as standard dose in Asian patients.

scholarly journals Effectiveness and safety of oral anticoagulants in elderly patients with atrial fibrillation

Heart ◽  
2021 ◽  
pp. heartjnl-2020-318753
Author(s):  
Ole-Christian Walter Rutherford ◽  
Christian Jonasson ◽  
Waleed Ghanima ◽  
Fabian Söderdahl ◽  
Sigrun Halvorsen
Keyword(s):  
Atrial Fibrillation ◽  
Elderly Patients ◽  
Major Bleeding ◽  
Standard Dose ◽  
Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Sensitivity Analyses ◽  
World Population ◽  
Systemic Embolism ◽  
Reduced Dose

ObjectivesTo assess the risk of stroke/systemic embolism (SE) and major bleeding associated with the use of oral anticoagulants in elderly patients with atrial fibrillation (AF) in a real-world population.MethodsWe identified all anticoagulant-naive initiators of warfarin, dabigatran, rivaroxaban and apixaban for the indication AF in Norway between January 2013 and December 2017. Multivariate competing risk regression was used to calculate subhazard ratios (SHRs) describing associations between non-vitamin K antagonist oral anticoagulants (NOACs) compared with warfarin for risk of stroke/SE and major bleeding.ResultsAmong 30 401 patients ≥75 years identified (median age 82 years, 53% women, mean CHA2DS2-VaSc score 4.5), 3857 initiated dabigatran, 6108 rivaroxaban, 13 786 apixaban and 6650 warfarin. Reduced dose was initiated in 11 559 (49%) of the NOAC-treated patients. For stroke, the SHRs for standard dose NOAC against warfarin were 0.80 (95% CI 0.57 to 1.13) for dabigatran; 1.07 (95% CI 0.89 to 1.30) for rivaroxaban and 0.95 (95% CI 0.78 to 1.15) for apixaban. For major bleeding, the SHRs against warfarin were 0.75 (95% CI 0.52 to 1.08) for dabigatran; 0.96 (95% CI 0.78 to 1.16) for rivaroxaban and 0.74 (95% CI 0.60 to 0.91) for apixaban. Comparing reduced doses of NOACs with warfarin yielded similar results. Sensitivity analyses were in accordance with the main results.ConclusionIn this nationwide cohort study of patients ≥75 years initiating oral anticoagulation for AF, standard and reduced dose NOACs were associated with similar risks of stroke/SE as warfarin and lower or similar risks of bleeding. The NOACs seem to be a safe option also in elderly patients.

Off-label underdosed apixaban use in Asian patients with non-valvular atrial fibrillation

2021 ◽  
Author(s):  
So-Ryoung Lee ◽  
Eue-Keun Choi ◽  
Sang-Hyun Park ◽  
Jin-Hyung Jung ◽  
Kyung-Do Han ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischaemic Stroke ◽  
Dose Reduction ◽  
Clinical Outcomes ◽  
Standard Dose ◽  
Composite Outcome ◽  
Claims Database ◽  
Off Label ◽  
Asian Patients ◽  
Hazard Ratios

Abstract Aims To compare the effectiveness and safety of off-label underdosed apixaban with on-label standard dose apixaban in Asian patients with atrial fibrillation (AF). Methods and results Using the Korean nationwide claims database, we identified patients who were prescribed apixaban and did not fulfil the dose reduction criteria for apixaban between January 2015 and December 2017. A multivariable Cox hazard regression model was performed, and hazard ratios (HRs) for ischaemic stroke, major bleeding (MB), all-cause death, and composite outcome were analysed. Compared to patients prescribed on-label standard dose apixaban (n = 4194), patients prescribed off-label underdosed apixaban (n = 2890) showed a higher risk of ischaemic stroke [adjusted HR (aHR) 1.38, 95% confidence interval (CI) 1.06–1.81], all-cause death (aHR 1.19, 95% CI 1.01–1.39), and the composite outcome (aHR 1.17, 95% CI 1.03–1.34), but with no significant differences in MB between the two groups. Among the patients who did not meet any dose reduction criteria, off-label underdosed apixaban use was associated with a significantly higher risk of ischaemic stroke than on-label standard dose apixaban use (aHR 1.85, 95% CI 1.25–2.73). Among the patients who met a single dose reduction criterion, off-label underdosed apixaban use was associated with a higher risk of all-cause death than on-label standard dose apixaban (aHR 1.32, 95% CI 1.07–1.64). Conclusion The off-label underdosed apixaban group showed higher risks of ischaemic stroke, all-cause death, and composite clinical outcomes than the on-label standard dose apixaban group, but both showed comparable risks of MB. Label adherence to apixaban dosing should be emphasized to achieve the best clinical outcomes for Asian patients with AF.

Off-label underdosed apixaban use in Asian patients with non-valvular atrial fibrillation

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
SR Lee ◽  
EK Choi ◽  
SH Park ◽  
JH Jung ◽  
KD Han ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Clinical Outcome ◽  
Dose Reduction ◽  
Standard Dose ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Off Label ◽  
Funding Sources ◽  
Asian Patients

Abstract Funding Acknowledgements Type of funding sources: None. Background In Asian patients with atrial fibrillation (AF), off-label underdosed prescriptions of direct oral anticoagulants (DOACs) are common Purpose We aimed to compare the effectiveness and safety of off-label underdosed apixaban with on-label standard dose apixaban in Asian patients with AF. Methods Using the Korean nationwide claims database, we identified patients who prescribed apixaban and did not fulfill the dose reduction criteria of apixaban between January 2015 and December 2017. Multivariable Cox hazard regression model was performed and hazard ratios (HRs) for ischemic stroke, major bleeding (MB), all-cause death, and the composite clinical outcome were analyzed. Results Compared to patients prescribed on-label standard dose apixaban (n = 4,194), patients prescribed off-label underdosed apixaban (n = 2,890) were associated with higher risks of ischemic stroke (adjusted HR [aHR] 1.38, 95% confidence interval [CI] 1.06-1.81), all-cause death (aHR 1.19, 95% CI 1.01-1.39) and the composite clinical outcome (aHR 1.17, 95% CI 1.03-1.34), but with no significant differences in MB between the two groups (Figure). In patients without any dose reduction criteria, off-label underdosed apixaban use was associated with a significantly higher risk of ischemic stroke than on-label standard dose apixaban use (aHR 1.85, 95% 1.25-2.73); however, in patients who had single dose reduction criteria (age ≥80 years, serum creatinine ≥1.5mg/dL, or bodyweight ≤60 kg), off-label underdosed apixaban use did not show a significant overall benefit in the composite clinical outcome compared with on-label standard dose apixaban, but was associated with a higher risk of all-cause death (aHR 1.32, 95% CI 1.07-1.64). Conclusion Off-label underdosed apixaban use was associated with higher risks of ischemic stroke, all-cause death, and composite clinical outcome and comparable risk of MB compared with on-label standard dose apixaban use. Label-adherence of apixaban dosing should be emphasized to achieve the best clinical outcome for Asian patients with non-valvular AF, especially in those without any dose reduction criteria. Abstract Figure.

scholarly journals Impacts of off-label dosing noacs on clinical outcomes in very elderly patients with atrial fibrillation

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
T Chao ◽  
Y.H Chan ◽  
G.Y.H Lip ◽  
S.A Chen
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Outcomes ◽  
Major Bleeding ◽  
Lower Risk ◽  
Oral Anticoagulants ◽  
Systemic Embolism ◽  
Very Elderly ◽  
Off Label ◽  
Funding Sources ◽  
Clinical Events

Abstract Background Studies about the comparisons of on-label and off-label dosing non-vitamin K antagonist oral anticoagulants (NOACs) regarding the risks of clinical outcomes among atrial fibrillation (AF) patients have been published. However, data among the very elderly AF patients were limited. In the present study, we aimed to investigate the impacts of inappropriate dosing of NOACs on clinical outcomes in AF patients aged ≥85 years of age. Methods We used medical data from a multi-center healthcare system in Taiwan enrolling 1,836 and 268 AF patients aged ≥85 years treated with NOACs and warfarin, respectively. Among 1,836 patients receiving NOACs, underdosing, overdosing and on-label dosing NOACs were prescribed in 248, 149 and 1439 patients, respectively. The risks of ischemic stroke/systemic embolism (IS/SE) and major bleeding were compared between warfarin and NOACs in different dosing groups. Also, the risks of clinical events of underdosing and overdosing NOACs were comapred to on-labeling dosing. Results Compared to warfarin, underdosing NOACs were associated with a higher risk of IS/SE (aHR 2.39; p=0.048) without a lower risk of major bleeding; while overdosing NOACs were not associated with a lower risk of IS/SE (aHR 0.74, p=0.604) (Figure 1). Compared to on-label dosing NOACs, underdosing NOACs were associated with a higher risk of IS/SE, while the risk was not lower for overdoing NOACs (Figure 2). Conclusions Even for very elderly AF patients aged ≥85 years, NOACs should still be prescribed at the dosing following the criteria defined in clinical trials and guideline recommendations. FUNDunding Acknowledgement Type of funding sources: None. Figure 1 Figure 2

scholarly journals Anticoagulation Challenges in Hematogeriatrics: Effectiveness and Safety of Direct Oral Anticoagulants Vs Vitamin k Antagonist in Elderly with Atrial Fibrillation

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1162-1162
Author(s):  
Desirée Campoy ◽  
Gonzalo Artaza ◽  
César A Velasquez ◽  
Tania Canals ◽  
Erik A Johansson ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Elderly Patients ◽  
Vitamin K ◽  
Major Bleeding ◽  
Frail Elderly ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Systemic Embolism ◽  
Bleeding Events

BACKGROUND Direct oral anticoagulants (DOAC) are increasingly used in patients with Non Valvular Atrial Fibrillation (NVAF) for stroke prevention. However, Follow-Up (FU) and dosing these agents in the elderly can be challenging due to different factors, such as chronic kidney disease, frailty, falls, multifactorial anemia and concomitant polypharmacy. These factors in elderly patients predisposes to both thromboembolic and bleeding events once atrial fibrillation occurs. Therefore, balancing risks and benefits of antithrombotic strategies in older populations is crucial. Despite recent increases in DOAC use in NVAF, there are still limited data regarding DOACs effectiveness and safety in frail elderly patients. AIM To assess the effectiveness and safety according to DOAC or Vitamin K Antagonist (VKA) in a cohort of elderly patients with NVAF. METHODS From April 2016 to April 2019, we consecutively included NVAF elderly patients (≥80 years-old) treated with DOAC or VKA in a prospective multicenter registry. Demographic, laboratory, frailty risk stratification and antithrombotic therapy data were collected. Patients had a minimum FU of 6 months. VKA patients had a standard FU through digital international normalized ratio (INR) control and the efficacy of therapy was determined by the time in therapeutic range (TTR) values from the preceding 6 months of treatment using Rosendaal's method. FU in DOAC patients was performed through structured and integral assessment following the Tromboc@t Working Group recommendations for management in patients receiving DOAC (Olivera et al, Med Clin 2018). Key practical management aspects are listed in the flow chart (Figure 1). Clinical Frailty Scale (CFS score) was assigned to each patient at the beginning and during the FU; patients were classified into three categories: non-frail (CFS 1-4), mild-to-moderately frail (CFS 5-6), and severely frail (CFS 7-9). RESULTS From a total of 1040 NVAF patients, 690 (63.5%) were treated with DOAC (61 dabigatran, 95 rivaroxaban, 254 edoxaban and 280 apixaban) and 350 with VKA. In the VKA group, the mean TTR was 52.8%. Demographic characteristics and CFS score are summarized in table 1. Kaplan-Meier analysis (median FU: 16.5 months) showed a significantly high incidence of stroke/systemic embolism among VKA patients vs DOAC patients (4.2 vs 0.5 events per 100 patient-years, p<0.001). Major bleeding in the DOAC group was significantly infrequent compared with VKA group (2.2 vs 8.9 events, p=0.001). In the DOAC group, 90% (n=20/22) of the major bleedings were gastrointestinal [16 rivaroxaban and 4 edoxaban]. However, in the VKA group 64% (n = 20/31) were gastrointestinal, 25.8% (n= 8/31) intracranial and 9.7% (n = 3/31) urogenital bleedings. We identified 365 very elderly patients (aged ≥ 90 years) of which 270 (39.1%) were DOAC patients and 95 (27.1%) VKA patients. In this subgroup of patients, after a multivariate regression analysis, the stroke/systemic embolism incidence was similar in both treatment groups regardless of the age, but major bleeding decreased significantly in DOAC group (adjusted HR 0.247, 95% CI 0.091-0.664). CONCLUSIONS Our data indicate that DOACs can be a good therapeutic option for stroke/systemic embolism prevention in frail elderly patients, showing low rates of stroke as well as bleeding events when a structured and integral FU is applied to anticoagulated patients. Further investigations are necessary to analyze the impact in the quality of life and net clinical benefit of anticoagulant therapy when a FU program is applied in elderly patients. Disclosures Sierra: Novartis: Honoraria, Research Funding, Speakers Bureau; Astellas: Honoraria; Pfizer: Honoraria; Daiichi-Sankyo: Honoraria, Speakers Bureau; Abbvie: Honoraria, Speakers Bureau; Roche: Honoraria; Jazz Pharmaceuticals: Honoraria.

scholarly journals The risk of stroke/systemic embolism and major bleeding in Asian patients with non-valvular atrial fibrillation treated with non-vitamin K oral anticoagulants compared to warfarin: Results from a real-world data analysis

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242922
Author(s):  
Oh Young Bang ◽  
Young Keun On ◽  
Myung-Yong Lee ◽  
Sung-Won Jang ◽  
Seongwook Han ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Practice ◽  
Vitamin K ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Systemic Embolism ◽  
Real World Data ◽  
Level Of Evidence ◽  
Warfarin Group ◽  
Asian Patients

Background Although randomized trials provide a high level of evidence regarding the efficacy of non-vitamin K oral anticoagulants (NOACs), the results of such trials may differ from those observed in day-to-day clinical practice. Aims To compare the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) between NOAC and warfarin in clinical practice. Methods Patients with non-valvular atrial fibrillation (NVAF) who started warfarin/NOACs between January 2015 and November 2016 were retrospectively identified from Korea’s nationwide health insurance claims database. Using inpatient diagnosis and imaging records, the Cox models with inverse probability of treatment weighting using propensity scores were used to estimate hazard ratios (HRs) for NOACs relative to warfarin. Results Of the 48,389 patients, 10,548, 11,414, 17,779 and 8,648 were administered apixaban, dabigatran, rivaroxaban and warfarin, respectively. Many patients had suffered prior strokes (36.7%, 37.7%, 31.4%, and 32.2% in apixaban, dabigatran, rivaroxaban, and warfarin group, respectively), exhibited high CHA2DS2-VASc (4.8, 4.6, 4.6, and 4.1 in apixaban, dabigatran, rivaroxaban, and warfarin group, respectively) and HAS-BLED (3.7, 3.6, 3.6, and 3.3 in apixaban, dabigatran, rivaroxaban, and warfarin group, respectively) scores, had received antiplatelet therapy (75.4%, 75.7%, 76.8%, and 70.1% in apixaban, dabigatran, rivaroxaban, and warfarin group, respectively), or were administered reduced doses of NOACs (49.8%, 52.9%, and 42.8% in apixaban, dabigatran, and rivaroxaban group, respectively). Apixaban, dabigatran and rivaroxaban showed a significantly lower S/SE risk [HR, 95% confidence intervals (CI): 0.62, 0.54–0.71; 0.60, 0.53–0.69; and 0.71, 0.56–0.88, respectively] than warfarin. Apixaban and dabigatran (HR, 95% CI: 0.58, 0.51–0.66 and 0.75, 0.60–0.95, respectively), but not rivaroxaban (HR, 95% CI: 0.84, 0.69–1.04), showed a significantly lower MB risk than warfarin. Conclusions Among Asian patients who were associated with higher bleeding risk, low adherence, and receiving reduced NOAC dose than that provided in randomised controlled trials, all NOACs were associated with a significantly lower S/SE risk and apixaban and dabigatran with a significantly lower MB risk than warfarin.

scholarly journals Possibilities of Using Rivaroxaban in Elderly Patients with Atrial Fibrillation: Data from Randomized Studies and Real Clinical Practice

2018 ◽  
Vol 14 (4) ◽  
pp. 575-582
Author(s):  
N. M. Vorobyeva ◽  
O. N. Kacheva
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Practice ◽  
Elderly Patients ◽  
Major Bleeding ◽  
Age Groups ◽  
Minor Bleeding ◽  
Systemic Embolism ◽  
Risk Of Death ◽  
Coronary Syndrome ◽  
Real Clinical Practice

The possibility of rivaroxaban using in elderly patients with non-valvular atrial fibrillation is discussed in the review. The results of ROCKET-AF randomized trial, including subgroup analysis in patients older than 75 years, are presented. The problem of unreasonable prescription of low doses of anticoagulants in real clinical practice and questions of adherence of patients to anticoagulant therapy are discussed. The results of two recent studies of actual clinical practice performed in patients over the age of 80 and 85 years, respectively, are presented as well as favorable profile of the efficacy and safety of rivaroxaban in these age groups. Rivaroxaban reduced the risk of stroke/systemic embolism by 38% and ischemic stroke by 41% with a comparable risk of major bleeding in patients older than 80 years. In another study, in patients older than 85 years in the rivaroxaban group, a 11% reduction in the risk of death from all causes, a reduction in the risk of major bleeding by 10% and an acute coronary syndrome by 14%, with similar risk of stroke/systemic embolism, clinically significant minor bleeding and a combined endpoint (stroke/systemic embolism, large bleeding, death from all causes) have been found.

P4769Optimal rivaroxaban dose in Asian patients with atrial fibrillation and normal or mildly impaired renal function

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
E.-K Choi ◽  
S R Lee ◽  
K D Han ◽  
J H Jung ◽  
S Oh ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Renal Function ◽  
Ischemic Stroke ◽  
Clinical Outcome ◽  
Major Bleeding ◽  
Impaired Renal Function ◽  
Gi Bleeding ◽  
Nonsignificant Trend ◽  
Off Label ◽  
Asian Patients

Abstract Background Although rivaroxaban 15 mg was only given to patients with creatinine clearance (CrCl) <50mL/min in the pivotal clinical trial, this dose has been commonly prescribed in Asian patients with non-valvular atrial fibrillation (AF) regardless of renal function. There is a paucity of information regarding the clinical outcomes of rivaroxaban 15 mg compared to rivaroxaban 20 mg in patients with CrCl ≥50mL/min. This study aimed to examine the effectiveness and safety of two doses of rivaroxaban in Asian patients with AF and CrCl ≥50mL/min. Methods Using the Korean National Health Insurance Service database, patients with AF and normal or mildly impaired renal function (CrCl ≥50mL/min) and naïve to rivaroxaban or warfarin were included from January 2014 to December 2016. Three separate 1:1 propensity score-matched cohorts were conducted: rivaroxaban 20 mg (R20) vs. warfarin (n=15,584), rivaroxaban 15 mg (R15) vs. warfarin (n=11,554), and R20 vs. R15 (n=10,392). Hazard ratios (HRs) for ischemic stroke, intracranial hemorrhage (ICH), gastrointestinal (GI) bleeding, major bleeding, all-cause death, and composite clinical outcome were analyzed. Results Among the pooled total study population, mean age was 66.9±10.9 years, 62.2% were male, mean CHA2DS2-VASc score was 3.16±1.79, and mean CrCl was 83.6±42.0 mL/min (median 78.4 mL/min, IQR 67.7–91.0 mL/min). A substantial proportion (42.6%) of patients with CrCl ≥50 mL/min were prescribed off-label R15 for stroke prevention in the Korean AF population. Compared to warfarin, both R20 and R15 showed significantly lower risk for ischemic stroke, major bleeding (mainly through reduction of ICH), and all-cause death (Figure). Overall, both R20 and R15 had better results for the composite clinical outcome compared to warfarin (HR: 0.617, 95% CI: 0.550–0.691 for R20, and HR: 0.759, 95% CI: 0.675–0.853 for R15). Compared to off-label R15, on-label R20 showed a nonsignificant trend toward lower risks of ischemic stroke, hospitalization for GI bleeding, hospitalization for major bleeding, and all-cause death. Overall, on-label R20 had better results for the composite clinical outcome compared to off-label R15 in patients with CrCl ≥50 mL/min (HR: 0.852, 95% CI: 0.735–0.988). This benefit was consistently observed in patients aged ≥80 years and those <50 kg. In patients with CrCl 50–60 mL/min, R20 showed a nonsignificant trend toward a higher risk of hospitalization for major bleeding compared to R15 (HR: 1.828, 95% CI 0.994–3.452). Conclusions Among Asians with AF and CrCl ≥50mL/min, both R20 and R15 were associated with reduced risk of ischemic stroke, ICH, major bleeding, and all-cause death without significantly increased risk of GI bleeding compared with warfarin. In patients with CrCl ≥50mL/min, on-label R20 showed better results for the composite clinical outcome compared to off-label R15.

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